Abstract
The DAX-1 gene encodes an orphan nuclear hormone receptor essential for normal fetal development of the adrenal cortex. Recently, DAX-1 has been shown to act as a transcriptional repressor of steroidogenic acute regulatory protein gene expression (StAR), suppressing steroidogenesis. We, therefore, investigated the expression of DAX-1 in a variety of adrenocortical tumors and compared the results with StAR mRNA expression. We found low or absent DAX-1 expression in aldosterone-producing adenomas (n = 11: 35 +/- 11%; normal adrenals: 100 +/- 17%) and in aldosterone-producing adrenocortical carcinomas (n = 2: 24 and 36%). Cortisol-producing adenomas showed intermediate DAX-1 expression (n = 8; 92 +/- 16), as did 3 non-aldosterone-producing carcinomas (72, 132 and 132%). High DAX-1 expression was present in nonfunctional adenomas (n = 3; 160 +/- 17%). In contrast to DAX-1, StAR mRNA expression did not show significant variations between groups. We did not detect the expected negative correlation between DAX-1 and StAR in adrenocortical tumors. These data suggest that high DAX-1 expression in adrenocortical tumors is associated with a non-functional phenotype whereas low DAX-1 expression favors mineralocorticoid secretion. These effects on steroidogenesis are mediated by mechanisms other than repression of StAR gene expression. Our results indicate that DAX-1 may be one of the factors influencing the steroid biosynthesis of adrenocortical neoplasms.
Original language | English |
---|---|
Pages (from-to) | 2597-600 |
Number of pages | 4 |
Journal | The Journal of clinical endocrinology and metabolism |
Volume | 83 |
Issue number | 7 |
DOIs | |
Publication status | Published - Jul 1998 |
Keywords
- Adolescent
- Adrenal Cortex Hormones
- Adrenal Cortex Neoplasms
- Adrenocortical Adenoma
- Adrenocortical Carcinoma
- Adult
- Aged
- Analysis of Variance
- Case-Control Studies
- Child
- Child, Preschool
- DAX-1 Orphan Nuclear Receptor
- DNA-Binding Proteins
- Female
- Gene Expression Regulation, Neoplastic
- Humans
- Infant
- Male
- Middle Aged
- Receptors, Retinoic Acid
- Repressor Proteins
- Steroids
- Transcription Factors